4{40 -{8 (diiodomethyl)sulfonyl{9 {0 acetanilide

ABSTRACT

Diiodomethylsulfones of the formula   WHEREIN N IS AN INTEGER FROM ZERO TO FOUR AND R is anilamido.

United States Patent [191 Crovetti Dec. 17, 1974 4 (DIIODOMETHYL)SULFONYL] ACETANILIDE [75] Inventor: Aldo Joseph Crovetti, Lake Forest,

[73] Assignee: Abbott Laboratories, North Chicago, Ill.

[22] Filed: Aug. 7, 1973 [21] Appl. N0.: 386,233

Related ILLS. Application Data [60] Continuation of Ser. No. 215,949, Dec. I6, 1971, abandoned, which is a division of Ser. No. 805,846, March 10, 1969, Pat. No. 3,632,859.

FOREIGN PATENTS OR APPLICATIONS 2,011,052 l H1970 Germany 260/397.6

Primary Examiner-Henry R. Jiles Assistant ExaminerS. D. Winters Attorney, Agent, or FirmRobert L. Niblack; Joyce R. Krei [57] ABSTRACT Diiodomethylsulfones of the formula wherein n is an integer from zero to four and R is anilamido.

1 Claim, No Drawings l I (D UEEQN M,QEFNIHPE, ROSS-REFERENC E TO RELATED APPLICATION DETAILED DESCRIPTION OF THE INVENTION This invention relates to novel substituted halo- 1 methyl sulfones and particularly to compounds wherein the substituents are higher alkyl, aryl and substituted aryl groups. The compounds are useful as fungicides.

Fungi areplants comprising molds, mildews, rusts, smuts and mushrooms and range in size from microscopic cells such as yeasts to highly organized fruiting bodies. While some fungi such as mushrooms are useful, many of them produce undesirable decay and destruction of paper, wood, textiles, grains and the like. Because fungi are found in association with such a large variety of host materials which differ sharply in their resistance to fungicides, there is a continuing need for diverse types of agents for fungus control.

It is an object of this invention therefore to provide compounds which are highly effective in the control of fungus particularly cellulose consuming mildew. It is a further object of this invention to provide, as fungicides, higher alkyl halomethyl sulfones, aryl and substituted aryl halomethyl sulfones.

These and other objects which will be apparent from the following description are attained through the provision of a compoundof the formula wherein R is selected from the group consisting of higher alkyl, cycloalkyl, t-butylphenyl, anilino, anilamido, loweralkoxyphenyl, naphthyl, nitrophenyl, halonitrophenyl, nitroloweralkylphenyl, polyloweralkylphenyl haloloweralkylphenyl, and halophenyl wherein the halogen is selected from the group consisting of fluorine, bromine and iodine, and n is an integer from to 4, when X, Y and Z have a total molecular weight greater than 110 and are selected from the group consisting of hydrogen and halogen; and wherein R is selected from the group consisting of chlorophenyl and polychlorophenyl when X, Y and Z have a total molecular weight greater than 250 and are selected from the group consisting of hydrogen and halogen.

The term loweralkyl" as used in the present specification and claims designates a straight chain orbranched chain alkyl group containing 1 to 4 carbon atoms; the term higher alkyl" designates an alkyl group of to carbon atoms.

The compounds of the present invention are prepared by. halogenating the R-sulfonyl acetic acids or their esters. Two schemes for preparation of the acids are presented below and illustrate reaction sequences and intermediate compounds where R=methoxyphenyl. Sulfonyl acetic acids with other R substituents may be prepared similarly.

mc-o-G-omoooom l LiAlHi (ether) .nico-@cmcnier lHSCHzCOOH Hi0 o-Qomomsomcoon Bra, reams/1.0 l cHicoiH h Hi0 o-cmor1i cHiooori '(M.P., 116-118) aio-oomoa=om i CH..COSH

HaC- O CH2CHzC HgSH (B.P., 85-:ss/0.4) iClCHflCOOH Hi0 o-oHicHioHis 011,00 OH i i Hi0 o--oHicHicHi oHic OOH o (M.P., 113-115) Melting points in degrees C.

The R-sulfonyl acetic acids or their esters are halogenated with sodium hypohalite in an alkaline aqueous solution followed by decarboxylation. The reaction may be represented as follows:

wherein X represents the halogen. The diand trihalomethyl compounds may be similarly prepared by employing larger proportions of the halogenating reagent.

In an alternative procedure, the aryl thioa cetic acids Many of these compounds are active against mildew, Chaetomium globosum at concentrations of 10 ppm, the lowest concentration at which they were tested; otherswere less active and up to 1,000 ppm were required. Larger concentrations may of course be used if the economics of the application permit. V

The activity of the compounds against fungus appears to be directly related to the total molecular weight of the halogen atoms on the methyl sulfone group. Thus, the greatest activity is exhibited by the iodomethyl sulfones and they are a preferred embodiment of this invention.

Fungicidal activity also appears to be enhanced when the value of the integer n was larger than 0 and in a pre ferred embodiment n is equal from 1 to 3 The following examples will illustrate the preparation of the compounds of this invention but should not be regarded as limiting.

Calculated for C H,,Br O S:

Found:

EXAMPLE [I p-BROMOPHENYL-TRIBROMOMETHYL SULFONE p-Bromophenyl-tribromomethyl sulfone was prepared according to the procedure of Example 1, but a proportionately larger quantity of bromine was used. The presence of the dibromomethyl and tribromomethyl moiety of the compound of Examples I and 11 was confirmed with NMR spectra.

EXAMPLE 111 p-METHOXYPHENYL DIIODOMETHYL SULFONE p-Methoxyphenyl diiodomethyl sulfone was prepared 5 by dissolving 11.5g (0.05 mole) of p-methoxyphenylsulfonyl acetic acid in 40 ml of 5% aqueous sodium hydroxide (0.05 mole). A solution of sodium hypoiodite was prepared by adding iodine monochloride, 19.5 g (0.12 mole) to 200 ml 5% sodium hydroxide solution.

The hypoiodite was added to the stirred sulfonyl acetic acid solution at room temperature and after the addition was completed, this mixture was stirred for 2 hours. It was then acidified with 22 ml concentrated HCl solution and stirred another two hours at room temperature while carbon dioxide evolved. The mixture was made alkaline with 50% sodium hydroxide solution and stirred for minutes. The tan product was filtered off, washed with water, triturated with sodium bisulfite solution to remove color, filtered and washed again. The crude dried p-methoxyphenyl diiodomethyl sulfone weighed 18.5 g and was crystallized from acetone-water, melting point 1324.

Calculated for C H I Q S: 21.93%; H=1.84%; l=57.95%

Other compounds of this invention prepared according to like procedures are:

4-(methy1 amido)-pheny1-diiodomethyl sulfone M.P. 214-216 C. 4-aminophenyl diiodomethyl sulfone M.P. 180-182 C. 4ch1oropheny1 diiodomethyl sulfone M.P. 132-134 C. 4bromopheny1 diiodomethyl sulfone M.P. 132-133 C. 2-mcthy1-4-chlorophenyl diiodomethyl sulfone MP. 1 10-1 11 C. alphanaphthyl diiodometh 1 sulfone M.P. 138-141 C. 2-mcthyl-4-bromophenyl iiodomethyl sulfone M.P. 114-115 C. 3-mcthy1-4-bromophenyl diiodometh 1 sulfone M.P. 136-139 C. 2,4-dimethylpheny1 diiodomethyl sul one M.P. 1 14-117 C. 3,4-dichlorophenyl diiodomethyl sulfone M.P. 144-146 C. 4-chlorophenyl dibromomethyl sulfone M.P. 112-1 16 C 4-methoxyphcnyl dibromomethyl sulfone M.P. -83 C. 4-ch1oropheny1 tribromomethyl sulfone M.P. 160-162 C 4-methoxyphcnyl tribromomethyl sulfone M.P. 134-137 C 2-mcthyl-4-t-butylphcnyl diiodomethyl sulfone M.P. 127-128 C 2-nitro-4-methylphenyl dibromomethyl sulfone M.P. 153-154 C 2-nitro-4-methy1phenyl tribromomethyl sulfone M.P. 183-186 C 2-nitro-4-methy1pheny1 iodomethyl sulfone M.P. 132-140 C 4-chlorubenzyl iiodomethyl sulfone M.P. 138-l4l C 2-nitro-4-chlorophcnyl iodomethyl sulfone M.P. 183-184 C 2-nitro-4-ch10ropheny1 tribromomethyl sulfone M.P. 185 C. 4-nitrophenyl diiodomethyl sulfone M.P. 184-186 C 2-mcthyl-4-t-butylpheny1 tribromometh 1 sulfone M.Pv 137-138 C 2-nitro-4-chlorophcnyl diiodomethyl su fone M.P. 160-162 C. 4-nitropheny1 tribromomethyl sulfone M.P. 197-199 C. 4-ch1orobenzy1 iodomethyl sulfone M.P. 219-220 C.

cyclohexyl diiodomethyl sulfone M.P. 126-128 C. n-octyl diiodomethyl sulfone M.P. 72-74 C. 4-fluorobenzyl diiodomethyl sulfone M.P. 1 19-12l C. 4-bromobcnzyl diiodomethyl sulfone M.P. 149-151 C. 4-mcthoxybenzyl diiodomethyl sulfone M.Pv 168l70 C. 3-ch1orobenzy1 diiodomethyl sulfonc M.P.. 182l84 C. 3,5-dimcthyl diiodometh 1 sulfone M.P. 188190 C. 1-Ehcny1-2-(diiodomethy sulfon l)ethane M.P. 69-71 C. 3- romobenzyl diiodomethyl su fone M.P. 192-194 C. 2-naphthy1methy1-diiodomethyl sulfone M.P. 172-174 C. 1-phenyl-3-(diiodomethylsulfonyl )propane M.P. 68-70 C. 3.4-dimcthylbenzyl diiodomethyl sulfone M.P. 175-184" C. 2,2,4,4-tetramethylbutyl diiodomethyl sulfone M.P. 101-103 C. 4-fluoro-benzyl dibromomethyl sulfone M.P. -1 17 C. 3-chlorobenzyl dibromomethyl sulfone M.P. ISO-152 C. 4-bromobenzyl dibromomethyl sulfone M.P. 1 6-128 C. 3.4-dichlorobenzy1 dibromomethyl sulfone M.P. 130-132 C. 2.4-dichlorobenzy1 dibromomethyl sulfone M.P. 109-1 1 1 C. 3-bromobenzy1 dibromomethyl sulfone M.P. 151-153 C. Z-bromobenzyl dibromomethyl sulfone MP. 1 10-1 12 C. 4-nitrobenzy1 dibromomethyl sulfone M.P. 151-153 C. 4-mcthox benzyl dibromomethyl sulfone M.P. 127 C. 2.5-dimet ylbenzyl dibromomethyl sulfone M.P. 119121 C. 3.4-dimcthylbcnzyl dibromomethyl sulfone MP. 1 18-125 C. l-phenyl-2-( dibromomethylsulfonyl )ethane oil) 1-phcnyl-3-(dibromomcthylsulfonyl )propane M.P. 55-57 C cyclohex ldibromomcthyl sulfone M.P. 96-98 C. n-decyldl ronromethyl sulfone M.P. 47-49 C n-hexudecyl dibromomethyl sulfone M.P. 76-78" C n-dccyl diiodomethyl sulfone M.P. 71-79 C. 2-chlorohenzy1 dibromomethyl sulfone M.P. 107-108" C.

6 The following example will illustrate the antifungal TABLE I-Contfnued properties of representative examples of the com- Comm. pounds of this invention. The characters R, n, and X, compound inhiiiit Y and Z correspond to those shown in Formula 1. .number R n XYZ globosom EXAMPLE W 5 14 CH 0 mini In this example, a nutrient medium containing a predetermined concentration of the test compound was NO;

inoculated with the fungus, incubated and then read to 15 0 Hm L000 determine the extent of growth of the fungus. The nu- 1O Q trient meduim employed was Saborauds liquid medium with 1.5% agar added and was autoclaved for 15 minutes at 15 pounds pressure. 16 0 H11 10 The inoculum, in this instance Chaetomium globosum HaC-C ATCC 6025, slant grown at 28 C for 7 days on a star- 15 1130/ vation medium (4% dextrose, 1% yeast extract, and 1.5 grams agar per liter of water) was scraped and sus- 17 1 HH 10 pended in approximately 2 ml Saborauds broth. The g?- TABLE I 20 18 0 11 10 Con entra- '3??? C m ound i g er R n XYZ globosom 1 0 H11 10 1 0 HBrBr 1,000

2 u 0 H11 10 2o H3o\ 0 H11 10 aO 3 Cinlizi 0 HH 1,000 l r a: 4 t 0 1, p usp nsion was adjusted to equal the N0, 1

s Farlands Standard Nephalometer tube using Saborauds broth as a diluent. 5 S 0 H11 10 The fungicidal compound was prepared by weighing 50 mg of material into a 0.25 ml of dimethylformamide 6 0 HII 10 and then diluted to 10 ml with water. An amount of fungicide solution sufficient to provide 1,000 ppm, 100 7 1 1m 10 ppm and 10 ppm, respectively, was added to sterile petrie dishes and 10 ml of nutrient medium agar was added to each and mixed thoroughly. The inoculum 8 0 H11 10 was applied with a cotton swab and, after three days in- HZNT cubation at 28 C, the plates were read for growth or 9 O H 0 ml 100 absence of growth of the fungus. The results are re- II I ported in Table l.

HSCCTN All of the compounds listed in Table l inhibit the 10 u 0 BrBrBr 100 growth of C. globosunt at L000 ppm and that many of H=C0@ the compounds of this invention completely inhibit fungus growth at a concentration as low as 10 ppm, the

11 0 H11 10 lowest concentration tested.

0 Without additional examples, it is believed that one skilled in the art, from the foregoing description is en- V abled to use this invention to its fullest extent.

BrBrBr 10 I claim:

l. A compound of the formula 

1. A COMPOUND OF THE FORMULA 